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Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinson's disease.
Vallerga, Costanza L; Zhang, Futao; Fowdar, Javed; McRae, Allan F; Qi, Ting; Nabais, Marta F; Zhang, Qian; Kassam, Irfahan; Henders, Anjali K; Wallace, Leanne; Montgomery, Grant; Chuang, Yu-Hsuan; Horvath, Steve; Ritz, Beate; Halliday, Glenda; Hickie, Ian; Kwok, John B; Pearson, John; Pitcher, Toni; Kennedy, Martin; Bentley, Steven R; Silburn, Peter A; Yang, Jian; Wray, Naomi R; Lewis, Simon J G; Anderson, Tim; Dalrymple-Alford, John; Mellick, George D; Visscher, Peter M; Gratten, Jacob.
Afiliação
  • Vallerga CL; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Zhang F; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Fowdar J; Griffith Institute for Drug Discovery (GRIDD), Griffith University, Brisbane, Australia.
  • McRae AF; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Qi T; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Nabais MF; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Zhang Q; University of Exeter Medical School, Exeter EX2 5DW, Devon, UK.
  • Kassam I; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Henders AK; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Wallace L; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Montgomery G; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Chuang YH; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Horvath S; Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
  • Ritz B; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
  • Halliday G; Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
  • Hickie I; Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
  • Kwok JB; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Pearson J; Department of Environmental Health, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
  • Pitcher T; Brain and Mind Centre & Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
  • Kennedy M; Brain and Mind Centre & Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
  • Bentley SR; Brain and Mind Centre & Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
  • Silburn PA; School of Medical Sciences, University of New South Wales, Sydney, Australia.
  • Yang J; Department of Pathology, University of Otago, Christchurch, New Zealand.
  • Wray NR; New Zealand Brain Research Institute, Christchurch, New Zealand.
  • Lewis SJG; Department of Medicine, University of Otago, Christchurch, New Zealand.
  • Anderson T; Department of Pathology, University of Otago, Christchurch, New Zealand.
  • Dalrymple-Alford J; Griffith Institute for Drug Discovery (GRIDD), Griffith University, Brisbane, Australia.
  • Mellick GD; Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
  • Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Gratten J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Nat Commun ; 11(1): 1238, 2020 03 06.
Article em En | MEDLINE | ID: mdl-32144264
An improved understanding of etiological mechanisms in Parkinson's disease (PD) is urgently needed because the number of affected individuals is projected to increase rapidly as populations age. We present results from a blood-based methylome-wide association study of PD involving meta-analysis of 229 K CpG probes in 1,132 cases and 999 controls from two independent cohorts. We identify two previously unreported epigenome-wide significant associations with PD, including cg06690548 on chromosome 4. We demonstrate that cg06690548 hypermethylation in PD is associated with down-regulation of the SLC7A11 gene and show this is consistent with an environmental exposure, as opposed to medications or genetic factors with effects on DNA methylation or gene expression. These findings are notable because SLC7A11 codes for a cysteine-glutamate anti-porter regulating levels of the antioxidant glutathione, and it is a known target of the environmental neurotoxin ß-methylamino-L-alanine (BMAA). Our study identifies the SLC7A11 gene as a plausible biological target in PD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Cromossomos Humanos Par 4 / Metilação de DNA / Sistema y/ de Transporte de Aminoácidos Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Cromossomos Humanos Par 4 / Metilação de DNA / Sistema y/ de Transporte de Aminoácidos Idioma: En Ano de publicação: 2020 Tipo de documento: Article